Osteoporose

1. Empfehlungen

2. Hilfsmittel

3. Ausblick

4. Anmeldung STZ

Absolutes Frakturrisiko mit Frax

Limitationen Frax

• Vorbehandelte Patienten

• Wirbelfrakturen

• Verlauf

Unterschiedliche Scores

Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial

Tsai J.N. et al. Lancet published online May 15, 2013

DATA-Studie: Denosumab und Teriparatid in Mono- oder Kombinationstherapie bei postmenopausaler Osteoporose

Design Offene, randomisierte, kontrollierte Studie 12 Monate Behandlung

Patienten 94 postmenopausale Frauen mit hohem Frakturrisiko (mittleres Alter: 66 Jahre)

Behandlung Entweder die Kombination Teriparatid 20ug täglich plus Denosumab 60mg alle 6 Monate oder jeweils mit einer der beiden Einzelnsubstanz allein im Verhältnis 1:1:1

Ausschluss-kriterien

• Vortherapie mit oralen BPs in den letzten 6 Monaten

• Vortherapie mit i.v. BPs oder Strontiumranelat

Endpunkte Prozentuale Änderung der DXA-BMD an der Gesamthüfte, Schenkelhals, LWS und 1/3 Radius nach 12 Monaten

Methodik:

Tsai et al. Lancet 2013

Tsai et al. Lancet 2013

Kombinierte Behandlung mit Denosumab und Teriparatid:die DATA-Studie > Änderungen der Knochenmineraldichte

Ergebnisse: Effekt auf Knochendichte nach 12 Monate

**

*

*

Ergebnisse:

BMD-Entwicklung nach 12 Monaten an der Lendenwirbelsäule

Kombinierte Behandlung mit Denosumab und Teriparatid:die DATA-Studie > Änderungen der Knochenmineraldichte

p-Wert

Dmab vs TPTD n.s.

Kombi vs TPTD 0,0005

Kombi vs Dmab < 0,0001

Kombination

TeriparatidDenosumab

Monate

LWS

BM

D-Ä

nd

eru

ng

(%

)

12600

2

4

6

8

10

Tsai et al. Lancet 2013

Ergebnisse:

BMD-Entwicklung nach 12 Monaten an der Hüfte

Kombinierte Behandlung mit Denosumab und Teriparatid:die DATA-Studie > Änderungen der Knochenmineraldichte

p-Wert

Dmab vs TPTD 0,003

Kombi vs TPTD < 0,0001

Kombi vs Dmab 0,0001

p-Wert

Dmab vs TPTD n.s.

Kombi vs TPTD < 0,001

Kombi vs Dmab 0,013

Kombination

Denosumab

TeriparatidBM

D-Ä

nd

eru

ng

(%

)

Monate

Schenkelhals

12600

1

2

3

6

4

5 Kombination

Denosumab

TeriparatidBM

D-Ä

nd

eru

ng

(%

)Monate

Gesamthüfte6

5

4

3

1

2

00 6 12

Tsai et al. Lancet 2013

DATA-Studie: Denosumab und Teriparatid in Mono- oder Kombinationstherapie bei postmenopausaler Osteoporose

Fazit:

Die Kombinationstherapie mit Teriparatid plus Denosumab erhöhte

die Knochendichte stärker als die jeweiligen Monotherapien an allen

gemessenen Stellen

Autoren suggerieren, dass diese Kombinationstherapie zu einem

additiven Effekt auf beide kortikalen und trabekulären Knochen führte

Diese Kombination könnte die Osteoporose-Behandlung bei

Patientinnen mit hohem Frakturrisiko verbessern

Tsai et al. Lancet 2013

International, multicenter, open-label, single-arm study

Key Inclusion Criteria: Completed the Pivotal Phase 3 Fracture Trial (completed their 3-year visit, did not discontinue

investigational product, and did not miss more than 1 dose). Not receiving any other osteoporosis medications.

Study DesignThe Pivotal Phase 3 Study – Extension

Pivotal Phase 3 Fracture Trial Extension Study

1 2 3Year 0 5 6 74 8 9 10

1 2 30 5 6 74Year

RANDOMIZATION

Denosumab 60 mgSC Q6M

(N = 3,902)

PlaceboSC Q6M

(N = 3,906)

ContinuedDenosumabTreatment

Cross-overDenosumabTreatment

Denosumab 60 mgSC Q6M

(N = 2,343)

Denosumab 60 mgSC Q6M

(N = 2,207)

Calcium and Vitamin D

SC = subcutaneous; Q6M = once every six monthsAdapted from Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.

Change in Lumbar Spine and Total Hip BMD Through 6 Years with Denosumab Treatment

The Pivotal Phase 3 Study – Extension

Data represents LS means and 95% CI. n = number of subjects with values at baseline and the time point of interest. *P < 0.05 vs Pivotal Phase 3 Study baseline; †P < 0.0001 vs Pivotal Phase 3 Study baseline and Extension baseline. ‡Represents subjects from the Pivotal Phase 3 Study DXA substudy. Orange numbers on the graphs represent the percent change in BMD while on denosumab treatment.

BMD = bone mineral density; CI = confidence interval; LS = least-squares; DXA = dual-emission X-ray absorptiometry Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.Cummings SR, et al. N Engl J Med. 2009;361:756-765.

2005 1485119‡ 122‡ 120‡ 122‡ 2028 1923Cross-over n 1962 1456118‡ 120‡ 2023 1998 2007 18962112 1588139‡ 141‡ 141‡ 142‡ 2148 2040Continued n 2086 1565139‡ 140‡ 2149 2125 2134 2016

Placebo Continued DenosumabCross-over Denosumab

Lumbar Spine BMD

*

–2

0

2

4

6

8

10

12

14

16

18

†

*

*

*

*

*

15.2%

Pe

rce

nt

Ch

an

ge

Fro

m B

as

eli

ne

1 2 3 4 50 6Study Year

†

†

†

†

†10.1% 9.4%

Pivotal Phase 3 Fracture Trial

ExtensionStudy

Total Hip BMD

*

–2

0

2

4

6

8

10

*

*

*

Study Year1 2 3 4 50 6

*

*

*

*

*

7.5%

†

††

†

†

†

5.7%

4.8%

Pivotal Phase 3 Fracture Trial

ExtensionStudy

Yearly Incidence of New Vertebral Fractures Through 6 Years

The Pivotal Phase 3 Study – Extension

n = number of patients with ≥1 fracture. N = number of randomized patients who remained on study at the beginning of each period and had available spine x-rays during the period of interest. *Annualized rate: (2-year rate)/2. Lateral radiographs (lumbar and thoracic) were not obtained at year 4 (year 1 of the Extension).

Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.Data on file, Amgen.

Yea

rly

Inci

den

ce o

f N

ew

Ver

teb

ral

Fra

ctu

re (

%)

Years of Denosumab Exposure

Fracture incidence was not evaluated as an efficacy endpoint in the extension study

Pivotal Phase 3 Fracture Trial Extension Study

Placebo Continued Denosumab Cross-over Denosumab

1898 35107 2482n 32 58 23341,6103,186 3,2473,400 3,4533,691N 3,702 2,101 1,5091,980

Yearly Incidence of Nonvertebral Fractures Through 6 Years

The Pivotal Phase 3 Study – Extension

n = number of patients with ≥ 1 fracture. N = of randomized patients who remained on study at the beginning of each period.Percentages for nonvertebral fractures are Kaplan-Meier estimates.Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.Data on file, Amgen.

Yea

rly

Inci

den

ce o

fN

on

vert

ebra

l F

ract

ure

(%

)

Years of Denosumab Exposure

Fracture incidence was not evaluated as an efficacy endpoint in the extension study

Pivotal Phase 3 Fracture Trial Extension Study

2,2433,454 3,4873,688 3,6823,906N 3,902 2,343 2,1052,207 2,0661,9642683 73103 75116n 98 32 3652 2429

Placebo Continued Denosumab Cross-over Denosumab

Neue Studien

Ernährung und Exercise: Do-Health, Frau Prof H.BischoffGeriatrie, ZAM, Senioren >70Medikamente: Anti-Sclerostin, Resultate in 2-3 Jahren,

Therapie:Therapiepause, Monitoring